Integration of Left-Right Pitx2 Transcription and Wnt Signaling Drives Asymmetric Gut Morphogenesis via Daam2

Welsh, Ian; Thomsen, Michael B; Gludish, David W.; Alfonso-Parra, Catalina; Bai, Yan; Martin, James F.; Kurpios, Natasza A.

doi:10.1016/j.devcel.2013.07.019

Cited by 79 publications

(94 citation statements)

References 61 publications

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“…Recent work suggests asymmetrical intestinal rotation is generated by LR differences in the dorsal mesentery that connects the midgut to the body wall -not in the gut tube itself, which remains symmetrical during the rotation process Kurpios et al, 2008;Welsh et al, 2013). By contrast, our results indicate that stomach curvature is driven by asymmetric morphogenesis within the organ itself.…”

Section: Pitx2 Controls Left Stomach Epithelial Morphogenesiscontrasting

confidence: 52%

Stomach curvature is generated by left-right asymmetric gut morphogenesis

et al. 2017

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Left-right (LR) asymmetry is a fundamental feature of internal anatomy, yet the emergence of morphological asymmetry remains one of the least understood phases of organogenesis. Asymmetric rotation of the intestine is directed by forces outside the gut, but the morphogenetic events that generate anatomical asymmetry in other regions of the digestive tract remain unknown. Here, we show in mouse and Xenopus that the mechanisms that drive the curvature of the stomach are intrinsic to the gut tube itself. The left wall of the primitive stomach expands more than the right wall, as the left epithelium becomes more polarized and undergoes radial rearrangement. These asymmetries exist across several species, and are dependent on LR patterning genes, including Foxj1, Nodal and Pitx2. Our findings have implications for how LR patterning manifests distinct types of morphological asymmetries in different contexts.

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Section: Pitx2 Controls Left Stomach Epithelial Morphogenesiscontrasting

confidence: 52%

Stomach curvature is generated by left-right asymmetric gut morphogenesis

et al. 2017

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“…The two aortic tubes move medially and fuse in the midline ventral to the notochord ( Figures 1C, 1D, and 1H-1J). In parallel, the mesenchymal cells medial to the CE meet in the midline ventral to the aorta ( Figures 1I, 1I 0 , and 1I 00 ), forming the dorsal mesentery (DM) (Figures 1J, 1J 0 , and 1J 00 ), which plays an essential role in subsequent gut looping and morphogenesis (Davis et al, 2008;Mahadevan et al, 2014;Welsh et al, 2013). In summary, at the beginning of the process of ventral body wall formation the embryo is flat and the aorta and notochord are in direct contact with the endoderm.…”

Section: Formation Of the Dorsal Mesentery And Ventral Body Structuresmentioning

confidence: 99%

Establishment of the Visceral Embryonic Midline Is a Dynamic Process that Requires Bilaterally Symmetric BMP Signaling

et al. 2016

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The vertebrate body plan contains both dorsal and ventral midline structures. While dorsal midline structures have been extensively studied, formation of ventral midline structures, and how they become aligned with the dorsal midline, is a fundamental aspect of vertebrate development that is poorly understood. This study uses the chick dorsal mesentery (DM) as a model for investigating the formation of ventral midline structures. We document formation of the DM by epithelial-to-mesenchymal transition (EMT) and medial ingression of the lateral plate coelomic lining and show that DM positioning is a fundamentally dynamic process regulated by relative levels of bone morphogenetic protein (BMP) signaling in the two sides of the ingressing lateral plate. Disruption of this process causes misalignment of the DM and disturbances during initial stages of lung morphogenesis. Since the dorsal midline is a source of BMP antagonists, these results suggest a mechanism for aligning the dorsal and ventral embryonic midlines.

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“…GRNs feed into specific proteins that harness physical forces such as tension and adhesion to control asymmetric bending and growth of internal organs [169]. Mechanical forces are critical for the rotation and looping of internal organs ( [170,171], see reviews for the heart in chick [172][173][174][175]).…”

Section: Physics Upstream and Downstream Of Transcriptional Networkmentioning

confidence: 99%

From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left–right patterning

McDowell

Rajadurai

Levin

2016

Phil. Trans. R. Soc. B

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One contribution of 17 to a theme issue 'Provocative questions in left -right asymmetry'. Consistent left -right (LR) asymmetry is a fundamental aspect of the bodyplan across phyla, and errors of laterality form an important class of human birth defects. Its molecular underpinning was first discovered as a sequential pathway of left-and right-sided gene expression that controlled positioning of the heart and visceral organs. Recent data have revised this picture in two important ways. First, the physical origin of chirality has been identified; cytoskeletal dynamics underlie the asymmetry of single-cell behaviour and patterning of the LR axis. Second, the pathway is not linear: early disruptions that alter the normal sidedness of upstream asymmetric genes do not necessarily induce defects in the laterality of the downstream genes or in organ situs. Thus, the LR pathway is a unique example of two fascinating aspects of biology: the interplay of physics and genetics in establishing largescale anatomy, and regulative (shape-homeostatic) pathways that correct molecular and anatomical errors over time. Here, we review aspects of asymmetry from its intracellular, cytoplasmic origins to the recently uncovered ability of the LR control circuitry to achieve correct gene expression and morphology despite reversals of key 'determinant' genes. We provide novel functional data, in Xenopus laevis, on conserved elements of the cytoskeleton that drive asymmetry, and comparatively analyse it together with previously published results in the field. Our new observations and meta-analysis demonstrate that despite aberrant expression of upstream regulatory genes, embryos can progressively normalize transcriptional cascades and anatomical outcomes. LR patterning can thus serve as a paradigm of how subcellular physics and gene expression cooperate to achieve developmental robustness of a body axis.This article is part of the themed issue 'Provocative questions in leftright asymmetry'.

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Integration of Left-Right Pitx2 Transcription and Wnt Signaling Drives Asymmetric Gut Morphogenesis via Daam2

Cited by 79 publications

References 61 publications

Stomach curvature is generated by left-right asymmetric gut morphogenesis

Stomach curvature is generated by left-right asymmetric gut morphogenesis

Establishment of the Visceral Embryonic Midline Is a Dynamic Process that Requires Bilaterally Symmetric BMP Signaling

From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left–right patterning

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